Apparatus and method for dynamic cooling of biological tissues for thermal mediated surgery

ABSTRACT

Dynamically cooling the epidermis of a port wine stain patient undergoing laser therapy permits maximization of the thermal damage to the port wine stain while at the same time minimizing nonspecific injury to the normal overlying epidermis. A cryogenic spurt is applied to the skin surface for a predetermined short period of time in the order of tens of milliseconds so that the cooling remains localized in epidermis while leaving the temperature of deeper port wine stain vessels substantially unchanged. The result is that epidermal denaturation and necrosis which normally occurs in uncooled laser irradiated skin sites does not occur and that clinically significant blanching of the port wine stains at the dynamically cooled sites establishes that selective laser photothermolysis of the port wine stain blood vessels is achieved. In addition, dynamic epidermal cooling reduces patient discomfort normally associated with flashlamp-pumped pulsed dye laser therapy.

This invention was made with Government support under Grant No.1R03RR6988-01 awarded by the National Institute of Health. TheGovernment has certain rights in this invention.

This is a continuation of application Ser. No. 08/222,976 filed on Apr.5, 1994 (now abandoned).

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to the field of laser surgery, and in particular,to the thermal treatment of biological tissues with laser pulses.

2. Description of the Prior Art

The illustrated embodiment of the invention is described below in thecontext of treatment of port wine stain birthmarks in human skin,although the scope of the invention is much broader in that it appliesto all types of thermal surgeries. A port wine stain is congenital,progressive, vascular malformation of the dermis involving capillariesand possibly perivenular nerves. Port wine stains occur in approximatelythree percent of one thousand live births. Although port wine stains maybe found anywhere on the body, they mostly appear on the face and arenoted over the dermatome distribution of the first and second trigeminalnerves.

In early childhood, port wine stains are faint pink macules, but thelesions tend to darken progressively to red-purple and by middle age,often become raised as a result of the development of vascular papulesor nodules and occasionally tumors. The hypertrophy of underlying boneand soft tissue occurs in approximately two-thirds of the patients withport wine stain, and serves to further disfigure the facial features ofmany children.

The prior art treatments for port wine stain includes scalpel surgery,ionizing radiation, skin grafting, dermabrasion, cryosurgery, tattooingand electrotherapy. Clinical results have been considered unsatisfactorydue to the cosmetically unacceptable scarring post treatment. All ofthese prior art techniques are no longer considered viable treatmentoptions for this reason.

A flashlamp-pumped pulsed dye laser offers a superior approach andtherapy due to its ability to selectively destroy cutaneous bloodvessels. Light passing through the epidermis is preferentially absorbedby hemoglobin which is the major chromophore in blood in the ectaticcapillaries in the upper dermis. The radiant energy is converted to heatcausing thermal damage and thrombosis in the targeted vessels. Prior artstudies have shown that the flashlamp-pumped pulsed dye laser producegood results in the vast majority of pediatric and adult patients.

Histopathological studies of port wine stains show a normal epidermisoverlying an abnormal plexus of dilated blood vessels located on a layerin the upper dermis as diagrammatically depicted in cross sectional viewin FIG. 1. The predominate endogenous cutaneous chromophores, absorbinglight at the 585 nanometer wavelength produced by flashlamp-pumpedpulsed dye laser, are melanin and hemoglobin. Therefore, the overlyingepidermal pigment layer comprises a barrier or an optical shield throughwhich the light must first pass to reach the underlying port wine stainblood vessels. The absorption of laser energy by melanin causeslocalized heating in the epidermis and reduces the light dosage reachingthe blood vessels, thereby decreasing the amount of heat produced in thetargeted port wine stains and leading to suboptimal blanching of thelesion.

The ratio of heat generated in port wine stains to that of the epidermisis a measure of the relative heating of the port wine stain relative tothe epidermis. The best clinical results realized in a port wine stainpatient undergoing laser therapy are obtained when the patient's ratioof heat generated in the port wine stain to that in the epidermis isgreater than or equal to one. Unfortunately, for many lesions, thethreshold for epidermal damage following laser therapy is very close tothe threshold for permanent blanching of the port wine stain.

One prior art method which has been tried is the application of icecubes to the skin surface prior to laser treatment, B. A. Gilchrest etal., "Chilling Port Wine Stains Improves the Response to Argon LaserTherapy, " Plast. Reconstr. Surg. 1982; 69:278-83. However, thesetreatments have not proven entirely satisfactory, nor more importantlyled to an improved therapeutic response, that is improved blanching ofthe port wine stain.

Other prior art attempts to provide surface cooling of the epidermisusing plastic bags filled with ice placed on the skin surface for fiveminutes, compressed freon gas used during irradiation, or chilled waterspread directly on the area being irradiated have also been explored, A.J. Welch et al., "Evaluation of Cooling Techniques for the Protection ofthe Epidermis During ND-YAG Laser Irradiation of the Skin,"Neodymium-YAG Laser in Medicine, Stephen N. Joffe editor 1983. However,these studies were done with pig cadaver tissue and normally utilizedcooling periods of 2 to 14 seconds. The reported results with freon weregood in only 28.5 percent of the cases, in some cases, the skin surfacewas momentarily frozen, and in others, the freon jet was found toovercool the skin surface.

Therefore, what is needed is some type of methodology or apparatus whichcan be effectively used to uniformly provide positive results, namelyallowing treatment of deeper or selected layers of tissue withoutnonspecific damage to the upper or nonselected layers.

BRIEF SUMMARY OF THE INVENTION

The invention is a method for using dynamic cooling to performphotothermolysis of selected buried chromospheres in biological tissues.The method comprises the steps of cooling a selected portion of thebiological tissue to establish a predetermined dynamic temperatureprofile, and irradiating the first portion and a second portion of thebiological tissue to thermally treat the second portion of thebiological tissue while leaving the first portion of the biologicaltissue substantially undamaged. As a result, the second portion of thebiological tissue may be laser treated without damage to the firstportion.

The first portion of the tissue lies adjacent the second portion and thestep of irradiating the second portion comprises the step of irradiatingthe second portion of the biological tissue through the first portion.

In the illustrated embodiment the biological tissue is skin The firstportion is epidermis and the second portion is dermis lying beneathmelanin contained in the epidermis. The step of establishing apredetermined dynamic temperature profile establishes a dynamicallycooled profile substantially only in the epidermis.

The step of establishing a predetermined dynamic temperature profile isperformed by providing a cryogenic spurt to the biological tissue at asite which is later irradiated. The cryogenic spurt is comprised ofcryogenic droplets or a mist.

The method can be characterized as establishing a thermal heat sinkthermally coupled to the first portion of the biological tissue. Thestep of establishing a thermal heat sink comprises the step ofeliminating an air-to-surface insulating barrier at the first portion ofthe biological tissue.

The step of providing the cryogenic spurt to the first portion of thebiological tissue comprises the step of disposing a liquid at apredetermined cooled temperature onto the surface of the first portionof the biological tissue. The liquid has a boiling point below normaltemperatures of the first portion of the biological tissue and thecryogenic spurt has a time duration sufficient to provide approximatelya 40-50 degree Centigrade temperature drop at the surface of the firstportion of the biological tissue. The duration of the cryogenic spurt isof the order of tens of milliseconds.

The method may further comprise the step of reestablishing apredetermined dynamic temperature profile in the first portion of thebiological tissue after irradiation of the second portion of thebiological tissue. The step of reestablishing the predetermined dynamictemperature profile in the first portion of the biological tissue isperformed immediately after both the first and second portions of thebiological tissue are irradiated by applying more cyrogen to the firstportion immediately after the last treatment.

The invention is also an apparatus for laser treatment of biologicaltissue comprising a pulsed laser, and a controllable element forproviding a spurt of a cooling substance to an irradiation site on thebiological tissue. A timing control triggers the pulsed laser and thecontrollable element for triggering the pulsed laser to fire apredetermined laser pulse after the controllable element provides thespurt of cooling substance. As a result, the irradiation site of thebiological tissue is dynamically cooled to selectively allow lasertreatment of tissue portions of the irradiation site. In the illustratedembodiment the pulsed laser is a flashlamp-pumped pulsed dye laser. Thecontrollable element comprises a cryogenic reservoir and anelectronically controlled solenoid valve coupled to the cryogenicreservoir for adiabatically releasing a spurt of the cryogen over apreselected time period. The timing control comprises a digital delaygenerator. The time duration of the spurt of cooling substance isdetermined by a triggering delay generated by the digital delaygenerator coupled to the controllable element and to the pulsed laser.

Still more specifically the invention is a method of laser treating portwine stain birthmarks in human skin having an epidermis containingmelanin and a dermis containing the port wine stains. The methodcomprises the steps of dynamically cooling the epidermis such that onsetof a predetermined temperature profile within the epidermis is achievedwithin a time period substantially shorter than the thermal diffusiontime between the port wine stain in the dermis and the overlyingepidermis. The port wine stain in the dermis is irradiated through theepidermis for a time period sufficient to selectively destroy cutaneousblood vessels within the port wine stain. As a result, the port winestain is destroyed without substantial biological damage to theepidermis.

The invention and its various embodiments may be better visualized bynow turning to the following drawings wherein like elements arereferenced by like numerals.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is highly diagrammatic side cross sectional view of human skintissue having a port wine stain embedded in the dermis.

FIG. 2 is a graph illustrating the dynamic cooling temperature profilesand skin as a function of depth corresponding to 10 to 100 millisecondcryogenic spurts.

FIG. 3 is a simplified diagram showing use of the apparatus of theinvention to conduct the methodology of the invention.

FIG. 4 is an empirical graph of the skin surface temperaturemeasurements obtained using a fast infrared detector from adjacent portwine stain test sites on a human patient which has had the test sitedynamically cooled according to the invention.

FIG. 5 is a graph of the slin surface temperature measurements obtainedas in the case of FIG. 4 from a test site on the same patient in whichthe test site has had no cooling.

FIG. 6a is a photograph of a port wine stain test site in a humanpatient having three rows of exposed sites in which the upper row isuncooled and the lower two rows dynamically cooled according to theinvention. FIG. 6a shows the skin 10 minutes after the laser exposure.

FIG. 6b is a photograph of the test sites of FIG. 6a as seen 10 daysafter laser exposure.

FIG. 6c is a photograph of the test sites of FIGS. 6a and 6b six monthsafter laser exposure.

The invention and its various embodiments can now be understood in termsof the following detailed description.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Dynamically cooling the epidermis of a port wine stain patientundergoing laser therapy permits maximization of the thermal damage tothe port wine stain while at the same time minimizing nonspecific injuryto the normal overlying epidermis. A cryogenic spurt is applied to theskin surface for a predetermined short period of time in the order oftens of milliseconds so that the cooling remains localized in epidermiswhile leaving the temperature of deeper port wine stain vesselssubstantially unchanged. The result is that epidermal denaturation andnecrosis which normally occurs in uncooled laser irradiated skin sitesdoes not occur and that clinically significant blanching of the portwine stains at the dynamically cooled sites establishes that selectivelaser photothermolysis of the port wine stain blood vessels is achieved.In addition, dynamic epidermal cooling reduces patient discomfortnormally associated with flashlamp-pumped pulsed dye laser therapy.

It is believed that all previously tried methods for cooling laserirradiated sites to prevent epidermal damage have essentially failed dueto the thermal response of skin to prolonged cooling in which a nearsteady state temperature distribution is achieved. In steady state orprolonged cooling, the internal temperature increases linearly from theskin surface down into the subcutaneous layers. Therefore, in additionto cooling the epidermis, prolonged cooling also reduces the ambienttemperature of the lower lying port wine stain blood vessels. Anyincrease in the threshold for epidermal damage achieved by temperaturereduction is almost entirely offset by the additional energy required toheat the port wine stain blood vessels to a sufficient temperature toobtain selective laser photothermolysis.

With dynamic cooling according to the invention, the epidermis can beselectively cooled. When a spurt of cryogen is applied to the skinsurface for an appropriately short period, that is on the order of tensof milliseconds, the cooling remains localized in the epidermis whileleaving the temperature of deeper port wine stain vessels unchanged.See, for example, FIG. 2, which is a graph of the dynamic coolingtemperature profiles in skin as a function of depth for 10 to 100microsecond cryogenic spurts. The vertical scale is shown in degreesCentigrade, while the horizontal scale is the depth in the tissue inmillimeters.

Region 10 generally represents the position of the epidermal melanin.Region 12 diagrammatically depicts the typical depth at which port winestains are found. Curve 14 is the temperature profile immediately aftera 10 millisecond cryogenic spurt applied to the test site as describedbelow. Curves 16, 18, 20 and 21 are the temperature profiles for 20, 30,50 and 100 millisecond cryogenic spurts, respectively. It can beappreciated that for cryogenic spurts of these durations substantiallyall of the temperature cooling which occurs is in the area of the skinabove port wine stain region 12. Meanwhile temperatures in port winestain region 12 are unchanged.

If the skin is dynamically cooled so that heat is removed at a constantrate, a heat flux F₀, the instantaneous skin temperature, T_(S), isgiven by the equation (1) ##EQU1##

Where z is the skin depth, T_(i) is the initial temperature at the skinsurface, K is the thermal conductivity, X is the thermal diffusivity anderfc is the complementary error function. From equation (1), thetemperature reduction of the skin surface in response to dynamic coolingcan be shown to be: ##EQU2##

Hence, surface temperature reduction is proportional to the heat flux,F₀, and the square root of the cooling time. For a given flux, theexposure time to the cryogenic spurt, t_(c), must be long enough toproduce a large ΔT₀, but short enough to avoid conductive cooling of theport wine stain vessels in region 12.

FIG. 3 is a highly diagrammatic depiction of one embodiment of theapparatus of the invention in which the methodology described above ispracticed. A test cryogen, which in the illustrated embodiment istetrafluoroethane, C₂ H₂ F₄ with a boiling point of -26.5 degreesCentigrade, and which is an environmentally compatible, nontoxic,nonflammable freon substitute, is used as a surface cooling agent. Shortcryogenic spurts of the order of tens of milliseconds are delivered ontothe skin surface through an electronically controlled solenoid valve 22,which valve is supplied with test cryogen from a cryogenic reservoir 24.

A fast infrared detector 26, which in the illustrated embodiment is anInSb 128×128 focal plane array detector, sensitive in the 3-5 micronspectral range, is used to measure the skin surface temperature before,during and after the cryogenic spurt and laser pulse. Detector 26 isused in the system of FIG. 3 as a means of verifying test results. It isto be understood that in a commercial embodiment of the invention,detector 26 may be omitted or a simpler and less expensive thermaldetector used in its place.

Detector 26 is triggered by a digital delay circuit 28 as manufacturedby Stanford Research Systems of Sunnyvale, Calif. Solenoid valve 22 issimilarly triggered at a time of -ΔT_(c) simultaneously with detector26. At a time t=0, a flashlamp-pumped pulsed dye laser 30 operating at awavelength of 585 nanometers with a pulse width of 450 microseconds istriggered.

The exposure time to the cryogenic spurt and the interval between theapplication of cryogenic spurts and the onset of the laser pulse arecontrolled by delay generator 28 and are usually less than 1millisecond. The cryogenic spurt released from solenoid valve 22 iscomprised of droplets of cryogen cooled by evaporation and mist formedby adiabatic expansion of vapor. Droplets of cryogen have been found toprovide a better heat sink that merely cooled gas. At the test site ofthe skin surface, the cryogenic spurt is made to cover an approximatecircular zone of about 7 millimeters in diameter concentric with thelaser spot which is approximately 5 millimeters in diameter. Clearly,the shape, size and disposition of the cooled region relative to theirradiated region can be varied according to the application in manyways consistent with the teachings of the invention.

The following results were obtained with human patients with port winestains subject to standard screening and consent protocols. Test siteswere selected and identified by a skin marker in a manner depicted inthe photographs FIG. 6a-c. Eighteen test sites were selected for eachpatient, six of which were irradiated without cooling and twelve ofwhich were irradiated with dynamic cooling of the invention. The siteswere selected on inconspicuous sectors of the port wine stain, forexample under the arm, which were generally representative of the entirelesion. The six sites selected for laser exposure with dynamic coolingwere irradiated by laser 30 at a maximum light dosage of approximately10 Joules per square centimeter. The other twelve test sites receivedidentical laser irradiation following a short cryogenic spurt of theorder of tens of milliseconds. Untreated areas of the port wine stainserved as a control, having no light exposure. The test sites wereobserved over the course of time to determine if any adverse effectsoccurred and if blanching of the port wine stain subsequently developed.Each of the subjects were evaluated initially to form a base line, andtwice a week for four weeks thereafter, and monthly through six monthsafter laser irradiation.

FIGS. 4 and 5 illustrate the skin surface temperature profiles whichwere measured using infrared detector 26 from one of the patient's portwine stain test sites, namely a test site that was cooled by an 80millisecond cryogenic spurt as shown in FIG. 4 and an uncooled test sitedepicted in FIG. 5. The graphs of FIGS. 4 and 5 were typical of all ofthe patients tested. The vertical scale in FIG. 4 is the skintemperature in degrees Centigrade and time scale is horizontally shownin milliseconds with the laser pulse occurring at time 0.

FIG. 4 shows that the skin surface temperature prior to laser exposurewas reduced for the cooled test site by as much as 40 degreesCentigrade. Therefore, the baseline skin surface temperature prior tolaser exposure was approximately -10 degrees Centigrade on the cooledsite as opposed to 30 degrees on the uncooled site. After a 10 Joule persquare centimeter light dosage from the laser, the skin surfacetemperature, just after time 0, for both the cooled and uncooled portwine stain sites, jumped 80 degrees Centigrade. However, because thebaseline skin surface temperature at the cooled site was initially minus10 degrees Centigrade, the maximum surface temperature achievedimmediately after laser exposure was 70 degrees Centigrade at the cooledsite as opposed to 110 degrees Centigrade at the uncooled site as shownin FIG. 5.

Infrared images of the uncooled test site taken by detector 26 show atemperature rise immediately after laser exposure with persistentsurface heating 90 milliseconds later indicating a slow dissipation ofheat trapped near the skin-air interface. Images taken by detector 26 ofa cooled site show lower surface temperatures observed immediately afterlaser exposure and the arrival of a delayed thermal wave at 90milliseconds after exposure as the heat generated in the port wine staingradually diffuses from the buried blood vessels toward the cooled skinsurface. Thus, the method of the invention also provides a means formeasuring the depth and size of the subsurface port wine stain vesselsusing a fast infrared detector.

FIG. 6a which was taken 10 minutes after laser exposure show blisteringindicative of thermal injury at the uncooled sites 34 and show in FIG.6b eschar formation indicative of epidermal denaturation and necrosis 10days after laser irradiation.

In contrast, no skin surface textural changes are noted at the cooledsites 36 in FIGS. 6a taken 10 minutes after exposure or in FIG. 6b 10days after exposure. Dynamic epidermal cooling permits exposure of portwine stain skin to an incident light dosage that was expected andsubsequently proven to cause epidermal damage at uncooled port winestain test sites. When the epidermis was rapidly cooled from ambientskin temperature at about 30 degrees Centigrade to minus 10 degreesCentigrade, immediately prior to laser exposure, no epidermal injury isnoted.

As shown in FIG. 6c, which is a photograph of the test sites of FIGS. 6aand 6b shown six months after exposure, clinically significant blanchinghas occurred at uncooled sites 34 and cooled sites 36. Blanching at thecooled sites indicates that selective laser photothermolysis did occur.Such blanching implies an adequate core temperature necessary to destroythe port wine stain blood vessels was achieved with the described lasertreatment. These results suggest the cooling following exposure to ashort cryogenic spurt of the order of tens of miliseconds ispreferentially localized to the epidermis, while the deeper temperatureof the port wine stain vessels remain unchanged.

Typically, port wine stain patients undergoing laser therapy with aflashlamp-pumped pulse dye laser report sensations like a "hot pinprick" or a "elastic band snapping against the skin." The discomfortlevel is energy dependent and increases with high light dosages and alsovaries with the sensitivity of the treated anatomical site. Paintolerance generally decreases with decreasing patient age. An additionaladvantage of dynamic epidermal cooling is reduction and in some cases,elimination of this discomfort. When the epidermis is rapidly cooledwith cryogenic spurts longer than 20 milliseconds immediately prior tothe laser exposure, the subjects in the present study reported feeling"nothing at all." Subjects treated with a cryogenic spurt as short as 5milliseconds report significant improvement to the level of comfortassociated with flashlamp-pumped pulsed dye laser therapy.

There are two reasons suggested for pain reduction reported by port winestain patients when using dynamic epidermal cooling prior to laserexposure. First, the maximum surface temperature achieved immediatelyafter laser exposure is lower and in some cases as much as 40 degreesCentigrade lower on the cooled site as compared to the uncooled site.Second, cryogen remaining on the skin evaporates and continues to removetrapped heat through the skin-air interface following laser irradiation.Therefore, the temperature of the post irradiated epidermis decreasesmore rapidly on the cooled site as compared to the uncooled site.

As stated above, the results of FIGS. 4 and 5 were obtained using an 80millisecond cryogenic spurt. However, similar surface temperaturereductions have been attained using shorter spurts. This suggests thatthe instantaneous temperature drop, T₀, prior to laser exposure is notthe only thermal effect responsible for the observed results. Even moreimportant is the rapid removal of heat from the epidermis after pulsedlaser exposure due to the establishment of a large temperature gradientnear the slin surface.

The heat loss from human slin in contact with air is insignificantbecause air is an excellent thermal insulator. With no cooling, heatdiffusing away from the absorbing melanin layer and port wine stainblood vessels builds up near the skin surface and produces an elevatedsurface temperature that persists for quite some time after laserexposure. Eventually, lateral thermal diffusion and cooling by bloodperfusion eliminates the heat built up near the surface, but this maytake several seconds.

It is believed that an important element in dynamic cooling is removalof heat that builds up near the skin surface by the evaporatingcryogenic liquid. Cryogen applied to the skin creates a heat sink belowthe surface of the skin that can remove heat before, during and afterlaser exposure. The heat sink persists for as long as the liquid cryogenremains on the skin surface. For any given cryogenic spurt, the size orcapacity of the sink is proportional to the area between thecorresponding temperature curve shown in FIG. 2 and a horizontal line atambient skin temperature with approximately 30 degrees Centigrade. Thisis represented in FIG. 2 as a striped area 38 for a 10 millisecondcryogenic spurt.

One goal then is to create with dynamic cooling a heat sink that canrapidly remove the trapped heat without cooling the port wine stainblood vessels in region 12. An important factor in drawing heat out ofthe skin is the temperature gradient that is established near the skinsurface. The steeper the gradient, the faster a given quantity of heatis withdrawn. Thus, to be successful, the cryogen should produce a largesurface temperature drop as quickly as possible. Moreover, the quantityof cryogen delivered can be controlled and thus, residual heat isremoved by cryogen that has remained on the skin surface after laserexposure. If additional heat must be removed, more cryogen can beapplied immediately after laser exposure. Thus, the present inventioncontemplates not only a cryogenic spurt immediately prior to laserexposure, but also one or more cryogenic spurts thereafter.

The complexity of the dynamic cooling process warrants a careful choiceof the cryogen and optimization of several cooling parameters. Accordingto the invention, the cryogen is selected based upon the followingfactors. The cryogen must have: (1) sufficient adhesion to maintain goodsurface contact with the skin; (2) a high thermal conductivity so theepidermis can be cooled very rapidly prior to laser exposure; (3) a lowboiling point to establish a large temperature gradient at the surface;(4) a high latent heat of vaporization to sustain evaporative cooling ofthe epidermis after laser exposure; and (5) no adverse health orenvironmental effects. Although the illustrated embodiment has describedthe use of tetrafluoroethane, many other cryogens could be substitutedwith similar results provided that they had one or more of the abovefactors in their favor.

Further, according to the invention, selectivity of the dynamic coolingof the epidermis can be optimized by controlling: (1) duration of thecooling spurt or spurts; (2) quantity of cryogen deposited on the skinsurface so that the effect of evaporative cooling can be maximized; and(3) timing of dynamic cooling relative to laser exposure.

Further, it is contemplated that application can be maximized using aportable hand piece which incorporates a laser fiber together with aminiature solenoid valve to time release cryogenic spurts onto the skin.In this case, single hand-held unit would be employed replacing solenoidvalve 22 and laser delivery hand piece 32 of FIG. 4. The use of a singleinstrument to provide both directed cryogenic sprays to selectively coolcertain areas of the skin relative to the irradiated spot and to providethe laser beam is expressly contemplated.

The importance of dynamic epidermal cooling has broad implications forthe development of future laser systems for port wine stain therapy.Currently, only a small proportion of patients are able to realize 100percent fading of their port wine stains even after undergoing multiplelaser treatments. One reason for treatment failure has been theinadequate heat generation within large port wine stain blood vessels. A450 microsecond pulse duration shown in the illustrated embodiment istoo short to generate sufficiently high core temperatures over longenough periods of time to destroy irreversibly large port wine stainblood vessels. An improved therapeutic outcome is expected for lasersystems utilizing the present invention with pulse durations of theorder of several milliseconds. Although longer pulse durations willcertainly destroy larger port wine stain blood vessels, such lasersystems will also produce greater epidermal injury due to nonspecificabsorption by melanin and heat dissipation from the injured vessels.Thus, it is within the scope of the invention to selectively cool andprotect the overlying epidermis during longer pulse exposures.

For example, in addition to repetitive patterns of pulsed cryogenicspurts on the laser site, the present invention contemplates thecontinuous washing of the laser site before, during and after the laserexposure. The protocol by which the cooling substance is applied tocreate the heat sink on the epidermis surface is not limited orrestricted in the invention as long as the time between the onset ofwhen the cooling of the epidermis occurs and the laser firing is shortwhen compared to the thermal diffusion time of the biological targetsought to be thermally destroyed, or in this case, the port wine stain.

Further, although the present invention has been described in thecontext of port wine stains, it must be specifically understood that theuse of dynamic cooling in conjunction with laser surgery can also bedirectly applied to many different applications in the field ofdermatology, such as laser treatment of tattoos, and epidermal anddermal melanoses; in the field of ophthalmology, such as cornea surgery;orthopedics and in the field of dentistry. The methodology and apparatuscan be applied in any case where it is important to maintain thetemperature or thermal damage to adjacent or overlying tissues at a lowlevel while heating or thermally impacting other target tissues.

Many alterations and modifications may be made by those having ordinaryskill in the art without departing from the spirit and scope of theinvention. Therefore, it must be understood that the illustratedembodiment has been set forth only for the purposes of example and thatit should not be taken as limiting the invention as defined by thefollowing claims. The following claims are, therefore, to be read toinclude not only the combination of elements which are literally setforth, but all equivalent elements for performing substantially the samefunction in substantially the same way to obtain substantially the sameresult. The claims are thus to be understood to include what isspecifically illustrated and described above, what is conceptionallyequivalent, and also what essentially incorporates the essential idea ofthe invention.

We claim:
 1. A method for performing laser treatment of biologicaltissues comprising the steps of:cooling a selected portion of saidbiological tissue for a predetermined first time period to establish apredetermined nonequilibrium dynamic temperature gradient through saidtissue so that substantially only said selected portion of saidbiological tissue is cooled by a predetermined minimum temperature drop,said predetermined dynamic temperature gradient being established byproviding a spurt of a predetermined amount of cryogenic liquid indirect contact with said biological tissue for said first time period ata site which is later irradiated for a predetermined second time period;and immediately after said first time period irradiating a superficialand deeper part of said selected portion of said biological tissue forsaid second time period to thermally treat said deeper part of saidbiological tissue while leaving said superficial part of said biologicaltissue substantially undamaged, said cryogenic liquid having a latentheat of vaporization, said superficial part of said biological tissuebeing cooled for said second time period by a change of state of saidcryogenic liquid to vapor, heat being quickly dissipated from saidsuperficial part of said biological tissue by means of supplying saidlatent heat of vaporization to said cryogenic liquid, said heat beingdissipated in an amount as determined by said predetermined amount ofcryogenic liquid applied to said superficial part of said biologicaltissue, the amount of dissipation of said heat from said superficialpart of said biological tissue being specified by said predeterminedamount of said cryogenic liquid applied to said superficial part of saidbiological tissue and by said latent heat of vaporization of saidcryogenic liquid, whereby said deeper part of said selected portion ofsaid biological tissue may be laser treated without damage to saidsuperficial part.
 2. The method of claim 1 wherein said superficial partis adjacent to said deeper part and said step of irradiating said deeperpart comprises the step of irradiating said deeper part of saidbiological tissue through said superficial part.
 3. The method of claim2 wherein said biological tissue is skin, said superficial part beingepidermis and said deeper part being dermis lying beneath melanincontained in said epidermis and wherein said step of establishing apredetermined dynamic temperature profile establishes a dynamicallycooled profile substantially only in said epidermis.
 4. The method ofclaim 1 wherein said cryogenic spurt comprises the step of disposingcryogenic droplets at said site.
 5. The method of claim 1 wherein saidstep of providing said cryogenic spurt disposes a cryogenic mist at saidsite.
 6. The method of claim 1 further comprising the step ofestablishing a thermal heat sink thermally coupled to said superficialpart of said biological tissue.
 7. The method of claim 6 where said stepof establishing a thermal heat sink comprises the step of substantiallyeliminating an air-to-surface insulating barrier at said superficialpart of said biological tissue.
 8. The method of claim 1 wherein saidstep of providing said cryogenic spurt to said superficial part of saidbiological tissue comprises the step of disposing a liquid at apredetermined cooled temperature onto the surface of said superficialpart of said biological tissue, said liquid having a boiling point belownormal temperatures of said superficial part of said biological tissueand wherein said first predetermined time period of said cryogenic spurthas a time duration sufficient to provide approximately a 40-50 degreeCentigrade temperature drop at said surface of said superficial part ofsaid biological tissue.
 9. The method of claim 8 wherein said durationof said cryogenic spurt is of the order of tens of milliseconds.
 10. Themethod of claim 1 further comprising the step of reestablishing apredetermined dynamic temperature profile in said superficial part ofsaid biological tissue after irradiation of said deeper part of saidbiological tissue, said superficial and deeper parts of said biologicaltissue being thermally coupled.
 11. The method of claim 10 wherein saidstep of reestablishing said predetermined dynamic temperature profile insaid superficial part of said biological tissue is performed immediatelyafter both said superficial and deeper parts of said biological tissueare irradiated by applying more cryogen to said superficial partimmediately after laser irradiation thereof.
 12. A method of lasertreating port wine stain birthmarks in human skin having an epidermiscontaining melanin and a dermis containing said port wine stainscomprising the steps of:dynamically cooling said epidermis by directlyapplying a controlled amount of a cryogenic liquid to said epidermissuch that onset of a predetermined nonequilibrium temperature profilewithin said epidermis is achieved within a first time periodsubstantially shorter than the thermal diffusion time between said portwine stain in said dermis and said overlying epidermis; and immediatelythereafter irradiating said port wine stain in said dermis through saidepidermis for a second predetermined time period sufficient in length toselectively destroy cutaneous blood vessels within said port wine stain,but for a time duration less than said thermal diffusion time betweensaid epidermis and dermis, simultaneously with said step of irradiating,rapidly cooling said epidermis by vaporizing said cryogenic liquid, saidamount of said cryogenic liquid applied to said epidermis beingcontrolled by offsetting a rate of cooling of said epidermis byvaporization of said cryogenic liquid against a rate of heating of saidepidermis by said step of irradiating; whereby said port wine stain isdestroyed without substantial biological damage to said epidermis. 13.The method of claim 12 wherein said epidermis is dynamically cooled bysubjecting said epidermis to a spurt of cryogen to establish apredetermined nonequilibrium temperature profile on said epidermiswithin said first predetermined time period.
 14. The method of claim 13wherein said first predetermined time period is of the order of tens ofmilliseconds.
 15. The method of claim 14 wherein said predeterminednonequilibrium temperature profile has a skin surface temperature of atleast approximately 40 degrees Centigrade below normal skin temperatureat the end of said first predetermined time period.
 16. A method forperforming laser treatment of biological tissues comprising the stepsof:cooling a first part of said biological tissue for a predeterminedfirst time period by direct contact of a liquid cryogen to said firstpart to establish a predetermined nonequilibrium dynamic temperaturegradient through said tissue so that substantially only said selectedportion of said biological tissue is cooled by a predetermined minimumtemperature drop, said predetermined dynamic temperature gradient beingdefined in said biological tissue for said first time period at a sitewhich is later irradiated for a predetermined second time period; andimmediately after said first time period, irradiating said first partand a second part of said biological tissue for said second time periodto thermally treat said second part of said biological tissue whileleaving said first part of said biological tissue substantiallyundamaged; and simultaneously with said step of irradiating, coolingsaid first part of said biological tissue for said second time period byquickly dissipating heat from said first part of said biological tissuethrough a thin layer of said liquid cryogen on said first part of saidbiological tissue at a rate high enough to prevent thermal-inducedbiological damage to said first part of said biological tissue; andquickly terminating said step of cooling to prevent any substantialremoval of heat from said second part of said biological tissue whichwould interfere with a thermal biological effect to said second part ofsaid biological tissue, whereby said second part of said selectedportion of said biological tissue may be laser treated without damage tosaid first part.
 17. A method for performing laser treatment ofbiological tissues comprising the steps of:applying a selected amount ofcooling cryogenic liquid in direct contact with a selected proximateportion of said biological tissue for a selected first time periodhaving a beginning and an end; irradiating said proximate portion andtargeted chromophores in a selected adjacent and distal portion of saidbiological tissue by a laser beam beginning from said end of saidselected first time period and continuing through a selected second timeperiod having a beginning and an end, said end of said selected firsttime period being controllable within a few milliseconds, and whereinsaid first time period is less than that required to substantially coolsaid targeted chromophores; and ending irradiation of said proximate anddistal portion of said biological tissue at said end of said selectedsecond time period, said end of said selected second time period beingcontrollable within a few milliseconds, and wherein said second timeperiod is less than that at which damage begins to occur in saidproximate portion, whereby said distal portion of said biological tissueis thermally surgically mediated without damage to said proximateportion.
 18. The method of claim 17 wherein said first time period isselected according to thermal dosage provided to said proximate portionof said biological tissue during said second time period, which firsttime period is adjusted according to individual patient characteristicsaffecting said thermal dosage to said proximate portion during saidsecond time period, and wherein said second time period is selected toprovide a thermal dosage to said targeted chromophores of said distalportion of said biological tissue, which thermal dosage is effective tosurgically mediate said targeted chromophores.
 19. The method of claim17 wherein said cryogenic liquid is applied to said biological tissue inliquid form by fine droplet spraying.
 20. The method of claim 17 whereinsaid steps of applying, irradiating, and ending irradiation areselectively repetitively performed according to patient characteristicswith a repetition rate controllable within a few milliseconds.